Publisher Health

Researchers at McMaster University have uncovered an unexpected role for a naturally occurring hormone already known for reducing appetite and supporting weight loss. The hormone appears to protect the liver from inflammation through a previously unknown signaling pathway, a finding that could point toward new approaches for treating advanced fatty liver disease.
The study, published in Cell Metabolism on August 10, 2026, found that GDF15 can reduce liver inflammation and slow the development of liver scarring even when weight loss does not occur. The result challenges the long-held view that the hormone’s benefits are primarily tied to its effects on appetite and body weight.
A New Target for Advanced Fatty Liver Disease
Millions of people around the world are affected by metabolic dysfunction-associated steatohepatitis (MASH), an advanced form of fatty liver disease that can eventually lead to cirrhosis, liver cancer, and liver failure. New weight loss medications have helped improve outcomes for many patients, but inflammation in the liver can remain even after substantial weight loss.
By identifying a biological pathway that directly regulates this inflammation, the new findings suggest that future therapies could potentially target liver inflammation alongside existing treatments focused on weight and liver fat.
“Our findings show that GDF15 does much more than regulate appetite and body weight,” says Gregory Steinberg, professor in McMaster University’s Department of Medicine, co-director of the Centre for Metabolism, Obesity and Diabetes Research (MODR), and senior author of the study. “We discovered that GDF15 activates a natural brain-to-liver signaling pathway that helps suppress liver inflammation and reduce fibrosis. This changes how we think about the hormone and suggests it may be part of the body’s own defense system against chronic liver injury.”
How GDF15 Sends a Protective Signal to the Liver
To explore how GDF15 affects advanced liver disease, the team used mouse models designed to closely reproduce human MASH. Researchers combined genetic, pharmacological, genomic, and spatial transcriptomics techniques to examine what happens when the hormone becomes active.

They found that GDF15 initiates signaling from the brain through the nervous system, ultimately causing the release of glucocorticoids. These steroid hormones are important for metabolism, immune activity, and the body’s response to stress.
The glucocorticoids then help suppress inflammation in the liver. Importantly, researchers observed these protective effects regardless of changes in food consumption, body weight or liver fat. GDF15 also appeared to slow the progression of liver fibrosis, the accumulation of scar tissue that occurs as liver disease becomes more advanced.
“GDF15 helps reprogram liver cells to reduce inflammation and scarring by advanced spatial technology,” says Dongdong Wang, first and corresponding author of the study and assistant professor in McMaster’s Department of Medicine. “Instead of causing liver damage, GDF15 appears to help calm the liver’s immune system. It shifts immune cells into a more protective and less active state, helping reduce inflammation and prevent damage to the liver.”
A Second Surprising Role for GDF15
Research published in 2023 by Steinberg and Wang showed that GDF15 helps the body maintain calorie burning during weight loss. The latest findings reveal a very different function for the same hormone: protecting the liver through a previously unknown anti-inflammatory pathway.
Researchers say that, taken together, the two studies could help shape future therapies that specifically address liver inflammation. This inflammation is a major factor driving the progression of MASH and remains difficult to treat.

Steinberg, an executive member of NexusHealth at McMaster and chief scientific officer, shareholder and co-founder of Espervita Therapeutics, recently co-authored preclinical research describing a promising drug candidate for advanced liver disease.
That research focused on a potential therapeutic compound. In contrast, the new study reveals a biological pathway that the body naturally uses to control liver inflammation, providing additional clues that could help guide the development of future treatments.
Combining Weight Loss With Inflammation Control
“Current therapies largely focus on reducing body weight and liver fat,” says Steinberg. “Our work suggests there may be value in combining those approaches with therapies that directly target inflammation. By understanding how the body naturally protects the liver, we can identify new opportunities to develop more effective treatments for people living with MASH.”
The study also included collaborators Rune E. Kuhre and Sebastian B. Jørgensen of Novo Nordisk A/S. The research was funded by the Natural Sciences and Engineering Research Council of Canada (NSERC), the Canadian Institutes of Health Research (CIHR), and Diabetes Canada. Novo Nordisk provided research support and supplied the GDF15 hormone used in the study.

Vaccines prevent serious illness for many people, but the immune protection they produce can differ substantially from one person to another. New research led by Arizona State University offers clues about what may be behind those differences.
The immune system may show signs of how strongly it will react even before vaccination. Researchers at ASU and collaborating institutions examined blood samples from more than 4,000 people, measuring antibodies that recognized 185 antigens. Those immune targets included common viruses and bacteria, along with targets connected to autoimmune diseases.
Artificial intelligence was then used to search for patterns in blood samples taken before and after COVID-19 vaccination. The analysis uncovered antibody signatures that could help separate people who produced strong vaccine responses from those whose responses were weaker.
The findings could eventually contribute to vaccination strategies tailored more closely to an individual’s immune system.
“What our study found is that certain biomarkers, when analyzed with AI, can predict who is likely to respond well to a vaccine, even before they receive it. This suggests that some people may be more immune-ready than others,” says Joshua LaBaer, who led the study.
LaBaer is executive director of the Biodesign Institute at ASU and director of the Virginia G. Piper Center for Personalized Diagnostics. The project also involved ASU researchers and collaborators from medical and research institutions around the United States.
The study appears in the current issue of the journal Cell Press Blue.

Blood Antibodies May Reveal Vaccine Readiness
Scientists typically evaluate vaccine response after vaccination by measuring whether the immune system generated antibodies against the intended target. In this study, the researchers approached the problem from the opposite direction. They wanted to know whether immune patterns already present in the blood could reveal how someone would respond before receiving a vaccine.
Many factors can influence vaccine response, including age, sex, genetics, previous illnesses and underlying health conditions. People with conditions that compromise the immune system are often more likely to produce weaker responses. However, vaccine outcomes can still vary widely among people who fall into the same general health categories.
The researchers used one of the first approaches to examine a broad antibody “fingerprint” present before vaccination as a measure of immune readiness. While some other prediction strategies depend on genetic testing, this method analyzes antibody patterns in blood, potentially making it easier to translate into clinical practice.
Health Status Alone Does Not Predict Response
To investigate whether these antibody fingerprints could signal vaccine readiness, the team measured immune responses to 185 antigens. The targets included SARS-CoV-2, the virus responsible for COVID-19, as well as other widespread viruses and bacteria and targets associated with autoimmune diseases.

Altogether, the researchers examined 8,687 samples from 4,089 participants. The group included healthy volunteers as well as people with diseases or treatments associated with immune suppression, including HIV, multiple myeloma, solid organ malignancy, autoimmune disease, inflammatory bowel disease and solid organ transplantation.
Several immunosuppressed groups were more likely to show reduced responses to COVID-19 vaccination. Yet simply placing someone into an immunosuppressed or healthy category did not reliably predict the outcome.
Some participants with suppressed immune systems still developed strong responses. At the same time, about 5% to 6% of healthy participants showed weak vaccine responses.
“Sentinel” Antibodies Signal Immune Readiness
Certain antibodies that were already present before vaccination stood out in the analysis. Higher levels of antibodies targeting common microbes, including Staphylococcus aureus, RSV and human respirovirus 3, were associated with stronger responses to COVID-19 vaccines.
The researchers call these “sentinel” antibodies because they may serve as indicators of a person’s underlying immune readiness. These antibodies are not necessarily acting directly against the vaccine target. Instead, their presence may provide information about how prepared the antibody-producing portion of the immune system is to mount a response.
The team also investigated whether the complete antibody fingerprint could provide more predictive information than a small number of individual biomarkers. A deep learning model examined patterns across the entire antibody panel, combining numerous measurements to build a broader picture of each participant’s immune state.
AI Searches Millions of Immune Signals
The results demonstrate one potential advantage of using AI in biomedical research. Machine learning systems can search millions of biological data points for subtle relationships that may be difficult to detect using conventional approaches.
In this case, the findings suggest that understanding vaccine readiness may require looking at the immune system as an interconnected whole instead of concentrating on one antibody or one disease.
The research also demonstrates the potential of newer technologies capable of measuring many antibody responses simultaneously. Rather than testing whether a person has antibodies against a single pathogen, researchers can examine a much broader immune landscape shaped by previous exposure to viruses, bacteria and other immune targets.
Toward More Personalized Vaccination
If the findings are confirmed in future studies and extended to additional vaccines, the approach could have uses well beyond COVID-19. Profiling sentinel antibodies might eventually support vaccine research, vaccine development and medical care for people who are especially vulnerable to weak immune responses.
Doctors could potentially use this type of information to identify people who might benefit from additional vaccine doses, more careful follow-up or other protective strategies. It could also give scientists a clearer understanding of why vaccination produces powerful immune responses in some people but weaker ones in others.
Ultimately, the research points toward a future in which vaccination decisions could be informed by an individual’s own level of immune readiness.

People who participate in colorectal cancer screening may face as much as a 43 percent lower risk of dying from the disease, according to new estimates published in JAMA Network Open by researchers at Karolinska Institutet and Umeå University in Sweden. The findings draw on as many as 14 years of follow-up data from the Stockholm-Gotland screening program.
Colorectal cancer is among the most common cancers, but outcomes are generally favorable when the disease is found early. Sweden has introduced universal screening, with people aged 60-74 offered testing every two years.
Participants receive a screening kit at home and are asked to provide a stool sample. The sample is checked for tiny amounts of blood that cannot be seen with the naked eye. If blood is found, additional testing is offered, most often a colonoscopy.
Long-Term Data Show a Larger Benefit
Stockholm and Gotland began routine colorectal cancer screening as early as 2008. Researchers from Karolinska Institutet and Umeå University have now tracked participants for up to 14 years to examine how screening may affect the risk of dying from the disease.
“A previous evaluation of the program showed that those who received an invitation to screening had a 14 percent lower risk of dying from the disease,” says Johannes Blom, senior consultant and associate professor at the Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, and the study’s corresponding author. “We have now been able to show that the mortality is significantly lower than that among those who actually take part in the screening.”
Participation Was Linked to a 43 Percent Lower Death Risk
The researchers compared people invited to screening between 2008 and 2012 with a control group whose members were either invited later or were not invited at all. They then used statistical methods to account for factors that could influence the findings, including people in the control group who later became eligible to participate and people who were invited but chose not to take part.

After those factors were considered, receiving an invitation to screening was associated with a 26 percent lower risk of dying from colorectal cancer. Among people who actually participated, the risk was 43 percent lower.
“Although screening is offered free of charge and the test is simple to carry out, around a third of people do not submit a sample,” says Johannes Blom. “Our study highlights the importance of taking part in colorectal cancer screening, and shows that it can actually save lives.”
More Than 376,000 People Were Followed
The study included 376,511 people. Over the follow-up period, researchers recorded 1,668 deaths from colorectal cancer.
The large number of participants, the lengthy follow-up period, and access to Swedish health registers were among the study’s key strengths. However, the researchers note that the estimates depend on statistical adjustments designed to account for different sources of bias, so some uncertainty remains.
The study was funded by the Swedish Cancer Society, the Swedish Research Council and Region Stockholm. The researchers state that they have no conflicts of interest.

Wellness habits you can start now – at no (or little) costImage source, Anastasiia MirraslavskaByFlorence Freeman, BBC News 

New Northwestern Medicine research published in Nature Communications suggests that a substance produced when gut bacteria digest dietary fiber may leave a durable molecular mark on cells lining the intestine. That imprint appears to promote immune tolerance and may help protect against inflammatory bowel disease-like conditions even after exposure to the metabolite has ended.
Yingzi Cong, PhD, the Stanley Gradowski Professor of Gastroenterology and a professor of Microbiology-Immunology and of Pathology, was senior and co-corresponding author of the study.
The researchers say the results support the idea that beneficial compounds made by gut microbes can effectively “train” the intestinal lining, helping it preserve immune tolerance over time.
“Our laboratory has long been interested in how the gut microbiota regulates immune responses at intestinal mucosal surfaces,” said first and co-corresponding author of the study Tianming Yu, PhD, research assistant professor of Medicine in the Division of Gastroenterology and Hepatology. “Short-chain fatty acids (SCFAs), which are produced by gut bacteria during the fermentation of dietary fiber, are known to have anti-inflammatory effects in the intestine.”
How Butyrate May Influence Gut Immunity
One major question, however, has remained unresolved, Yu said.
“A large proportion of butyrate in the gut is rapidly absorbed and metabolized by intestinal epithelial cells (IECs), which limits the amount of free butyrate that can directly reach underlying immune cells,” Yu said. “This led us to ask whether butyrate might act through IECs to regulate intestinal immunity.”
To investigate, the researchers supplied mice with butyrate in their drinking water for a set period and then ended the treatment. Two weeks after the butyrate had been withdrawn, CD4+ T-cells were still producing elevated levels of IL-10, an important anti-inflammatory cytokine that helps control intestinal inflammation.

The treated mice were also more resistant to chemically induced colitis. Compared with untreated animals, they lost less weight, had lower levels of inflammatory markers, and developed less severe tissue damage. According to the study, this protection depended on IL-10 signaling.
The researchers also determined that the lasting effect did not result from changes to the gut microbiome itself. In experiments involving germ-free mice, which lack all microbes, butyrate still created a persistent immune-regulating environment.
“We found that oral butyrate treatment induces a sustained immunoregulatory response in the intestine, characterized by increased IL-10 production in CD4+ T-cells and protection from intestinal inflammation even after butyrate treatment is stopped,” Yu said. “This effect was also observed in germ-free mice, suggesting that butyrate can establish a lasting intestinal environment that does not depend on continuous microbial stimulation.”
Intestinal Cells May Store a Lasting Biological Signal
Yu and his colleagues next focused on intestinal epithelial cells (IECs), which form the physical boundary between the body and the microbiome. In laboratory experiments, epithelial cells exposed to butyrate caused a strong increase in IL-10 production in both mouse and human T-cells.
“We further found that conditioned medium from butyrate-treated IECs strongly induced IL-10-producing CD4+ T-cells in both mouse and human T-cell culture systems,” Yu said. “These findings suggest that IECs secrete some immunoregulatory factors after butyrate treatment, and these factors can act on T-cells.”
The team then used metabolomic analysis to search for molecules that might be carrying this signal. One likely candidate was N1-acetylspermidine. The compound increased IL-10 production in T-cells and appeared to account for part of the immune-regulating activity generated by epithelial cells exposed to butyrate, Yu said.

“Mechanistically, we found that butyrate acts on IECs and induces sustained transcriptional and epigenetic activation of Sat1, an acetylpolyamine biosynthetic enzyme,” Yu said. “This promotes production of the metabolite N1-acetylspermidine, which contributes to the ability of butyrate-treated IEC-conditioned medium to induce IL-10 production in CD4⁺ T-cells.”
The results challenge the traditional idea that intestinal epithelial cells are primarily temporary responders whose main role is to serve as a barrier. Instead, the findings suggest that these cells may retain a longer-lasting molecular record of beneficial signals from the microbiome.
“The significance of this work is that it identifies a mechanism by which a microbiota-derived metabolite can create durable epithelial T-cell crosstalk,” Yu said. “The intestinal epithelium is often viewed as a short-lived barrier that responds rapidly to luminal stimuli. Our findings suggest that it can also retain a lasting imprint of a microbial metabolite signal. The study also introduces the idea that beneficial microbial metabolites may ‘train’ the IECs to maintain immune tolerance over time.”
Potential Implications for Inflammatory Bowel Disease
More research will be necessary to confirm the findings and determine whether the same mechanism operates in people, but Yu said the work could eventually have implications for inflammatory bowel disease.
“One important next step is to determine how this epithelial metabolic pathway operates in human intestinal disease, especially in patients with inflammatory bowel disease,” Yu said. “We are interested in testing whether the butyrate-Sat1-N1-acetylspermidine pathway is altered in human IECs and whether it correlates with immune regulation or disease activity.”
The researchers also intend to investigate other metabolites that may contribute to the effect. N1-acetylspermidine by itself did not fully account for all of the immune-regulating activity observed in the experiments.
Over the longer term, Yu said the findings may expand scientists’ understanding of the relationship among diet, metabolites produced by gut microbes and the intestinal lining.
“Many studies have focused on how inflammation can leave harmful memory in epithelial cells, but our findings suggest that beneficial microbial metabolites may also establish protective epithelial programs,” he said. “Understanding how diet, microbiota-derived metabolites and inflammation shape intestinal epithelial memory could open new directions for restoring intestinal immune tolerance in inflammatory bowel disease.”
Wenjing Yang, MD, PhD, research assistant professor of Medicine in the Division of Gastroenterology and Hepatology, was co-first author of the study.
Additional Feinberg co-authors include Suxia Yao, MD, research associate professor of Medicine in the Division of Gastroenterology and Hepatology; and Parambir Dulai, MD, associate professor of Medicine in the Division of Gastroenterology and Hepatology.
Cong, Yu, Yang, Yao, and Dulai are members of the Center for Human Immunobiology.
The study was supported by National Institutes of Health grants DK135193, DK124132 and DK145439.

For decades, medications for obesity typically delivered only modest reductions in body weight. That changed with the arrival of Ozempic and other GLP-1 therapies, which can produce sustained weight loss of 10 to 15% or more. Yet despite their remarkable effectiveness, scientists still do not fully understand what these medications are doing inside the brain.
New research from Yale has now uncovered an unexpected mechanism that challenges a long-standing view of the brain circuits involved in hunger and weight control. Scientists had generally thought that agouti-related peptide (AgRP) neurons, which are well known for stimulating hunger, worked mainly against weight loss. The new findings suggest something very different. During treatment with GLP-1 drugs such as Ozempic, these neurons appear to be recruited to help maintain fat loss.
“This completely changes how we think about the mechanism involved in these medications and provides new insight into the biology underlying their long-term effects, opening an avenue for the development of more efficient drugs,” said Mateus d’Ávila, a Ph.D. candidate in neuroscience working in Tamas Horvath’s lab in the Department of Comparative Medicine at Yale School of Medicine (YSM) and first author of the study.
The research was published in the journal Proceedings of the National Academy of Sciences (PNAS).
Why Ozempic Works So Well
Semaglutide, the active ingredient in GLP-1 medications such as Ozempic, has emerged as one of the most effective drugs ever developed to treat obesity. What has remained less clear is why its effects are so powerful and persistent.
Earlier generations of weight loss medications can reduce appetite nearly as effectively as semaglutide, yet they do not produce the same level of sustained weight loss. That difference led the Yale team to suspect that semaglutide must be doing more than simply making people or animals eat less.

One widely discussed explanation had been that GLP-1 medications cause weight loss by decreasing the activity of neurons responsible for promoting hunger. However, researchers had not directly tested the role of AgRP neurons during chronic GLP-1 treatment in vivo.
Testing the Brain’s Hunger Circuit
The Yale team set out to identify what was missing from that explanation. By studying how the brain responds and adapts during treatment, they hoped to uncover biological targets that could eventually lead to more effective obesity therapies.
Using a mouse model, the researchers combined several experimental approaches while tracking body weight, food consumption, metabolism, and energy expenditure during semaglutide treatment. They also used genetic techniques that allowed them to selectively eliminate or silence AgRP hunger neurons. This enabled the scientists to test whether those neurons were actually required for semaglutide to produce its lasting effects.
The results were striking. In mice genetically engineered to lack AgRP neurons, GLP-1 drugs were no longer able to sustain weight loss.
Additional experiments involving electron microscopy, molecular biology, and electrophysiology revealed another surprise. Rather than being suppressed by semaglutide, the AgRP neurons were activated.

Hunger Neurons Take an Unexpected Role
The researchers say the findings point to a more complicated response inside the brain than previously recognized. When GLP-1 treatment creates a calorie deficit, the brain appears to respond by increasing the activity of AgRP hunger neurons. Those same neurons also help coordinate the loss of fat.
In other words, cells traditionally viewed as obstacles to weight loss may actually become part of the biological machinery that allows GLP-1 therapies to maintain it. The finding adds a previously unknown layer to scientists’ understanding of how these medications work.
The experiments were conducted in mice, so further research will be necessary to determine whether the same mechanism operates in humans. Even so, identifying how GLP-1 medications influence the brain could provide an important foundation for developing the next generation of obesity treatments.
“By identifying a previously unrecognized neural mechanism involved in sustaining weight loss, our work provides new biological insights that could eventually help researchers design therapies that are even more effective or have fewer side effects,” d’Ávila said.
Other authors from YSM include Roberto Collado-Pérez, a postdoctoral associate; Zhong-Wu Liu, assistant professor adjunct; Joseph Schlessinger, the William H. Prusoff Professor of Pharmacology; and Horvath, the Jean and David W. Wallace Professor of Comparative Medicine.

Knee pain is a familiar problem for many people, particularly as they get older. Although persistent knee discomfort can have many causes, osteoarthritis is one of the most common.
Knee osteoarthritis develops as the cartilage that cushions the bones in the joint gradually breaks down. Healthy cartilage allows the knee to move smoothly while helping protect the bones. As this protective layer becomes thinner, pain and other problems can develop and may become more severe over time.
“Osteoarthritis can cause knee pain and stiffness, which can negatively impact a person’s activity level, risk of falling, mood and general quality of life,” said Dr. Abby Cheng, an orthopedic surgeon at Washington University School of Medicine in St. Louis who also specializes in physiatry, the nonsurgical treatment and rehabilitation of conditions such as arthritis.
Knee Osteoarthritis Can Affect More Than Mobility
The effects of osteoarthritis can extend well beyond pain in the joint. Difficulty moving can result in missed work and lost income. It can also discourage people from being physically active, which may increase their risk of chronic conditions including heart disease, cancer and diabetes.
Osteoarthritis is also extremely common. More than 30 million adults in the U.S. have some form of the condition, and the knee is the joint most frequently affected. Although osteoarthritis is often associated with older age, roughly half of cases occur among people who are still of working age.
“Having weak leg muscles and being overweight or obese increases a person’s risk for knee osteoarthritis,” Cheng said. “Women, older adults, people with a prior knee injury and those with a family history of osteoarthritis are also more likely to have the condition.”
Lifestyle Changes Can Help Ease Knee Pain

People who already have osteoarthritis have several options for managing pain and mobility problems. Healthy habits, along with medical treatments when needed, may also help slow the condition from getting worse.
“Eating more plants and less processed or sugary food reduces inflammation in the body, which can reduce pain from osteoarthritis in all joints,” Cheng said. “Other common treatments for knee osteoarthritis include strengthening the thigh muscles, using knee braces, taking anti-inflammatory medications, getting cortisone and other injections, and sometimes having knee replacement surgery.”
Health care providers can work with patients to develop individualized strategies for managing osteoarthritis. They can also connect people with programs and other resources that can make it easier to begin healthy changes and maintain them over time.
Small improvements can have a surprisingly large effect. Cheng noted that for a person who is overweight, losing 10 pounds can reduce the stress placed on the knees by 40 pounds with every step. That reduction in pressure can significantly ease joint pain.
Exercise and Healthy Weight May Lower Risk
Many of the strategies used to manage osteoarthritis may also help reduce the chances of developing it.

Regular physical activity is one of them. Despite the common belief that running damages the knees, running can be part of an active lifestyle aimed at lowering osteoarthritis risk. Maintaining a healthy weight can also reduce strain on the joints.
Diet matters as well. A healthy eating pattern rich in whole grains, fruits and vegetables, while limiting processed and refined foods, can support overall health and may help protect against osteoarthritis.
Family History Does Not Determine Your Future
Osteoarthritis differs from diseases such as cancer and heart disease, but its effects on health, well-being and quality of life can still be substantial. Millions of people live with the condition, yet there are practical steps individuals can take to reduce their own risk and potentially help protect the health of their families.
“Some people think that because a parent or grandparent had osteoarthritis, they will develop it too,” Cheng said. “And while it’s true that osteoarthritis can run in families, it doesn’t mean there’s nothing a person can do to successfully lower their risk of developing it.”
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Researchers, including a Rutgers professor, have gained a clearer view of the biological changes associated with schizophrenia by directly measuring synaptic connections in the living human brain. The team used specialized positron emission tomography (PET) imaging to examine these crucial points of communication between brain cells.
The study, published in Molecular Psychiatry, was led by senior authors Avram Holmes, associate professor of psychiatry at Robert Wood Johnson Medical School and core faculty member of the Center for Advanced Human Brain Imaging Research within the Rutgers Brain Health Institute, and Rajiv Radhakrishnan, associate professor of psychiatry and radiology and biomedical imaging at Yale University. First author Sidhant Chopra, formerly a postdoctoral fellow in the Holmes Lab, is a McKenzie Research Fellow at Orygen, Australia’s Centre of Excellence in Youth Mental Health, and the University of Melbourne in Australia.
Measuring the Brain’s Synaptic Connections
Synapses are tiny junctions that allow brain cells to communicate with one another across neural circuits. Problems involving these connections are believed to play a role in the cognitive and emotional symptoms of schizophrenia. Until now, however, scientists have had a limited understanding of exactly where synaptic loss occurs in the brains of living people because conventional imaging methods such as magnetic resonance imaging cannot specifically measure synapses.
The research involved 122 people, including 29 diagnosed with schizophrenia, making it one of the largest synaptic density PET imaging studies conducted so far. Compared with healthy participants, people with schizophrenia showed a pronounced and widespread reduction in synaptic connections across several parts of the brain. These included frontal and temporal regions as well as areas involved in memory and emotion. The loss was also considerably greater on the left side of the brain than on the right.
Researchers found that this synaptic pattern did not match the changes in brain volume typically seen with standard MRI scans. That distinction suggests synaptic loss and changes in brain volume may reflect separate biological processes rather than two imaging methods capturing the same underlying change.
A Molecular Pattern Behind Synaptic Loss
The team also discovered that the brain regions showing the greatest synaptic losses tended to contain high concentrations of receptors for important neurotransmitters, including serotonin, gamma-aminobutyric acid and glutamate. The finding suggests that the molecular characteristics of individual brain regions may influence how vulnerable they are to changes associated with schizophrenia.

To explore how synaptic loss might move through the brain, the researchers used computer simulations based on the brain’s structural connections. Their modeling identified an area in the left frontal lobe as a likely starting point from which synaptic loss could spread into connected regions.
“These findings suggest that in schizophrenia, synaptic loss is not random,” Chopra said. “Rather, it follows the brain’s molecular and connectivity architecture, which could eventually help identify where and how to intervene.”
“This detailed mapping of synaptic vulnerability could eventually help identify where and how to intervene to preserve or restore brain function, such as emerging therapies to prevent and regrow synapses,” Holmes added.
Toward More Precise Schizophrenia Treatments
The researchers said future work will build on these results by investigating how synaptic loss changes over time and how it responds to clinical treatments. A better understanding of that progression could ultimately help researchers develop more precise and personalized approaches to schizophrenia care.

Vaccine breakthrough stops cancer returning in trialImage source, Getty ImagesByJoe McFaddenHealth reporterPublished19 August 2026Updated 20 August 2026A new personalised vaccine given in combination with a drug has stopped skin cancer returning in patients during a trial, representing a potentially watershed moment in cancer treatment.The vaccine, developed by drug companies Merck & Co or MSD, and Moderna, was given to patients with high-risk melanoma, a type of skin cancer, after they had surgery.Early results show this new jab extended the length of time these patients were cancer free, but it’s unclear for how long, according to an announcement by the two firms.Cancer experts say this is a breakthrough, but emphasise caution as the full results have not been released or peer-reviewed whereby independent experts examine and check the trial findings.And even after the trials process has finished, the treatment would still need to be approved by regulators and then go through another approval process before it was made available on the NHS.The vaccine, called Intismeran, was given in combination with Keytruda, an immunotherapy drug already used in cancer treatment.Compared with taking the Keytruda on its own, the companies said taking the drug and vaccine together significantly increased the time patients remained cancer free and reduced the risk of the disease spreading to other organs.The phase three trial involved more than 1,000 patients who had high-risk stage two, three or four melanoma – meaning they ranged from having large tumours in a specific area to cancers which had already spread to other parts of the body.’Shows promise’Prof Peter Johnson, National Clinical Director for Cancer at NHS England, told the BBC’s Today Programme it was an exciting development. “Most of the cancer immune treatments we have been using up til now have been about cutting the immune system loose and hoping that it recognises the cancer. This [new treatment] is a way to direct it very specifically.”It feels like it’s a very important advance for us.” He said the NHS was preparing to bring this type of treatment to patients. Merck, known as MSD in Europe, and Moderna are calling this a personalised vaccine, meaning it works by targeting an individual patient’s tumour.In order to create this new jab, scientists used mRNA technology – which was used for some Covid-19 vaccines – to target specific mutations within the cancer cells by surgically removing a small part of a patient’s tumour and then sequencing its DNA.The result is a personalised anti-cancer jab which is specific to the patient’s tumour and instructs the immune system to recognise and attack any tumour cells that remain. The two companies are testing other similar personalised vaccines for lung, bladder and kidney cancers.Stephane Bancel, chief executive of Moderna, said the findings represent a “pivotal moment” in the field of cancer research.Shares in both Moderna and Merck have surged since the announcement,

Women are diagnosed with autoimmune diseases far more often than men, and new research from the Garvan Institute of Medical Research and UNSW Sydney may help explain why. Autoimmune diseases occur when the immune system mistakenly targets the body’s own healthy tissues. Lupus, for example, can affect as many as nine women for every one man, yet the genetic factors behind this striking difference have remained poorly understood.
Researchers have now identified more than 1,000 genetic switches that behave differently in female and male immune cells. These differences appear to contribute to greater activity in inflammation-related pathways in females, offering a new biological explanation for why women may be more susceptible to autoimmune disease.
The findings, published in The American Journal of Human Genetics, provide further evidence that diseases can develop and appear differently in males and females. They also reinforce the importance of including both sexes in medical research, which has historically depended heavily on male study groups.
“Our findings show that the immune system needs to be studied with sex in mind. Even though we know men’s and women’s immune systems differ, many studies still overlook these differences, which can limit how well we understand disease, and in turn bias treatment options,” says Garvan’s Dr. Seyhan Yazar, first author of the study.
Studying Immune Cells One at a Time
For years, researchers studying immune differences between the sexes were limited by technology. Traditional bulk blood analysis measures average activity across a mixture of many cells, which can hide important differences in the behavior of specific cell types.
New single-cell technologies have made it possible to examine individual immune cells in much greater detail. According to the researchers, this is the first study to investigate male and female immune differences at single-cell resolution on such a large scale.

The team sequenced more than 1.25 million peripheral blood mononuclear cells, which are immune cells circulating in the bloodstream, from nearly 1,000 healthy people. The participants belonged to the OneK1K cohort, a major Australian research project created to investigate how genetics affects individual immune cells across a large population.
Clear differences emerged when the researchers compared the cellular profiles of males and females. Males had larger proportions of monocytes, immune cells that serve as early responders to threats. Their gene activity was also more strongly focused on fundamental cell maintenance and protein production.
Females, by comparison, had greater numbers of B cells and regulatory T cells. Their immune cells also showed much more genetic activity associated with inflammatory pathways.
“While this highly reactive immune profile gives females an advantage in fighting viral infections, it comes with a biological trade-off: a greater predisposition to autoimmune diseases. On the other hand, male immune cells are less primed for inflammation, making men generally more susceptible to infections and non-reproductive cancers,” says co-senior author Dr. Sara Ballouz, Senior Lecturer at UNSW.
A more reactive immune system can provide valuable protection because it remains more prepared to respond to genuine threats. However, maintaining that heightened state of readiness may also increase the chance of immune “friendly fire,” in which the body mistakenly attacks its own healthy tissues and triggers autoimmune disease.
More Than 1,000 Genetic Switches Reveal a Hidden Pattern
Examining individual cells allowed the researchers to detect sex specific genetic differences that earlier studies using bulk blood samples could not see.

The team focused on genetic switches that function in one sex but not the other. Known as ‘expression quantitative trait loci’, these switches can be thought of as volume controls that influence how strongly particular genes are activated or suppressed.
Researchers have often assumed that differences between male and female immune systems are largely driven by the X and Y sex chromosomes. The new findings challenged that expectation.
The sex specific genetic switches were much less concentrated on the sex chromosomes than researchers anticipated. Instead, most were located on autosomes, the non sex chromosomes shared by males and females. In total, the researchers identified more than 1,000 sex specific genetic switches in these regions.
Genetic Clues to Why Lupus Affects More Women
Some of these genetic controls were directly associated with autoimmune disease.
The researchers identified particular variants that influenced the female-biased expression of two genes linked to systemic lupus erythematosus. The finding could help explain why lupus occurs about nine times more often in women than in men.
Genetics alone does not determine autoimmune risk. Other influences, including hormones, also play important roles. Even so, these genetic differences appear to establish a distinct biological starting point that could affect a person’s susceptibility to disease.
“This is the first time we have shown that these differences occur at the genetic control level, providing a new layer of insight into human immunity,” Dr. Ballouz says. “Having shown that female-biased genes are heavily enriched in inflammatory pathways, we now have another biological rationale for why the immune system can more easily mistakenly attack the body’s own tissues in women.”
Toward More Personalized Autoimmune Treatments
The findings could also have implications for people living with autoimmune conditions such as lupus. Current treatments do not work equally well for everyone, and many commonly used therapies broadly suppress immune activity throughout the body.
By identifying distinct genetic pathways involved in male and female immunity, the research points toward a future in which treatments could be more precisely targeted to a patient’s particular form of disease rather than broadly weakening the entire immune system.
“Our findings add strong evidence that female and male autoimmune diseases may not be the same, and the way we should treat them may not necessarily be the same. Currently, clinicians rely on a one-size-fits-all management approach for most autoimmune diseases — a more inclusive approach is needed,” says Dr. Yazar.
“If we want to realize the potential of precision medicine, we have to understand these fundamental biological variables,” says Professor Joseph Powell, co-senior author and Director of Garvan’s Translational Genomics Program. “Treatments need to be tailored not just to the disease, but to how a patient’s immune system operates at a baseline genetic level.”
Dr. Seyhan Yazar is a Conjoint Lecturer at St Vincent’s Clinical School, Faculty of Medicine and Health, UNSW Sydney. Dr. Sara Ballouz is Senior Lecturer in UNSW’s School of Computer Science and Engineering. Professor Joseph Powell is the Director of UNSW’s Institute of Genomics and Health.